Department of Physical Medicine & Rehabilitation and Pediatrics, Center for Epidemiology and Biostatistics, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229-3039, USA.
PM R. 2010 Jan;2(1):37-42. doi: 10.1016/j.pmrj.2009.10.010.
To evaluate the pharmacokinetics of amantadine in children with impaired consciousness from acquired brain injury.
Randomized, double-blind, placebo-controlled, crossover study with sparse sampling for pharmacokinetics.
Tertiary care pediatric hospital.
Children, ages 6-18 years, with impaired consciousness 5-10 weeks after acquired brain injury.
Subjects received amantadine for 3 weeks. Subjects were randomized to placebo or amantadine 4 mg/kg/day for 7 days followed by 6 mg/kg/day for 14 days. Crossover was after a 7-day washout period.
The Coma/Near-Coma Scale and Coma Recovery Scale-Revised were done 3 times per week to evaluate arousal and consciousness. Plasma concentrations of amantadine were determined for pharmacokinetic parameter estimation and evaluation of the exposure-response relationship. Adverse events were monitored.
Nine subjects met the final inclusion and exclusion criteria, 7 of whom agreed to participate. Five subjects completed both arms of the study. Amantadine total body clearance was 0.17 L/h/kg with a half-life of 13.9 hours. Higher exposure of amantadine (average concentration of amantadine during 6 mg/kg/day > 1.5 mg/L) may be associated with better recovery of consciousness.
Amantadine was well-tolerated in children with acquired brain injury and demonstrates pharmacokinetics similar to those reported for healthy young adults. Based on the preliminary data, higher dosing may be considered in the setting of brain injury.
评估 18 岁以下脑损伤后意识障碍儿童的金刚烷胺药代动力学。
随机、双盲、安慰剂对照、交叉研究，药代动力学采用稀疏采样。
三级儿科医院。
脑损伤后 5-10 周意识障碍的 6-18 岁儿童。
受试者接受金刚烷胺治疗 3 周。将受试者随机分为安慰剂或金刚烷胺 4mg/kg/天 7 天，然后 6mg/kg/天 14 天。洗脱期为 7 天。
每周 3 次进行昏迷/接近昏迷量表和昏迷恢复量表修订版评估觉醒和意识。测定金刚烷胺的血药浓度，以进行药代动力学参数估计和评估暴露-反应关系。监测不良事件。
9 名受试者符合最终纳入和排除标准，其中 7 名同意参加。5 名受试者完成了研究的两个阶段。金刚烷胺的全身清除率为 0.17L/h/kg，半衰期为 13.9 小时。更高的金刚烷胺暴露量（6mg/kg/天期间平均金刚烷胺浓度>1.5mg/L）可能与意识恢复更好相关。
金刚烷胺在脑损伤儿童中耐受性良好，药代动力学与健康年轻成人报告的相似。基于初步数据，在脑损伤情况下可以考虑更高的剂量。
